MODEL EXPERIMENTS ON SQUID AXONS AND NG108-15 MOUSE NEUROBLASTOMA X RAT GLIOMA HYBRID-CELLS

Three types of ionic current essentially determine the firing pattern of nerve cells: the persistent Na+ current, the M current and the low- voltage-activated Ca2+ current. The present article summarizes recent experiments concerned with the basic properties of these currents. Key nes and Meves (Proc R Soc Lond B (1993) 253, 61-68) studied the persis tent or steady-state Na+ current on dialysed squid axons and measured the probability of channel opening both for the peak and the steady-st ate Na+ current (PFpeak and PF35) was a function of voltage. Whereas P Fpeak Starts to rise at -50 mV and reaches a maximum at +40 to +50 mV, PFSS only begins to rise appreciably at around 0 mV and is still incr easing at +100 mV. This differs from observations on vertebrate excita ble tissues where the persistent Na+ current turns on in the threshold region and saturates at around 0 mV. Schmitt and Meves (Pfliigers Arc h (1993) 425, 134-139) recorded M current, a non-inactivating K+ curre nt, from NG108-15 neuroblastoma x glioma hybrid cells, voltage-clamped in the whole-cell mode, and studied the effects of phorbol 12,13-dibu tyrate (PDB), an activator of protein kinase C CPKC), and arachidonic acid (AA). PDB and AA both decreased I-M, the effective concentrations bring 0.1-1 mu M and 5-25 mu M. respectively; while the PDB effect wa s regularly observed, the M current depression by AA was highly variab le from cell to cell. The PKC 19-31 peptide, an effective inhibitor of PKC, in a concentration of 1 mu M almost totally prevented the effect s of PDB and AA on M current, suggesting that both are mediated by PKC . Schmitt and Meves (Pfliigers Arch (1994a) 426, SuppI R 59) measured low-voltage-activated (I-v-a) and high-voltage-activated (I-v-a) Ca2currents on NG 108-15 cells and investigated thr effect of AA and PDB on both types of current. At pulse potentials >-20 mV, AA (25-100 mu M ) decreased I-v-a and h-v-a I-Ca. The decrease was accompanied by a sm all negative shift and a slight flattening of the activation and inact ivation curves of the l-v-a I-Ca. The AA effect was not prevented by 5 0 mu M eicosa-5,8,11,14-tetraynoic acid (ETYA), an inhibitor of AA met abolism, or PKC 19-31 peptide and not mimicked by 0.1-1 mu M PDB. Prob ably, AA acts directly on the channel protein or its lipid environment . The physiological relevance of these three sets of observations is b riefly discussed.